The more I learn about science, the more awe I feel over the very existence of literally anything. Seriously. When you think about the world on an atomic level like I do, it is amazing to me that atoms come together to form molecules that eventually come to compose an entire person.
Nowhere is this more true than in human reproduction. The entire process of making a new person from conception to birth is both magical and entirely bizarre.
I’ve already talked about my own research interests in the female reproductive system through Part I of this series. However while attending the San Diego Glycobiology Symposium (SDGS) recently, I learned about an important sugar-based molecule that turns out to be essential to the function of a female reproductive-specific organ—placenta.
But before I can talk to you about placenta, I have to give you some background on malaria. Malaria of course is a deadly blood-borne disease that is spread by mosquitos in places like Africa and Asia. What actually causes the disease is a microbe called plasmodium that uses specialized proteins to attach itself to different structures on the surface of red blood cells. There are about sixty of these proteins and it takes children in Africa about fifteen years to develop antibodies to all of them. All of those antibodies essentially make them immune to the disease.
That is, until they become pregnant. For some reason, people who have already developed immunity against malaria become susceptible once again during their first and second pregnancies. While the malaria doesn’t always kill the hosts, it often kills the fetus. By the third pregnancy, the these people generally become immune again. No one really understood why this phenomenon was happening.
Then a team from Kenya realized that something on the plasmodium was binding very strongly to another something on the surface of cells in the placenta, an organ that helps support the growth of a fetus and only shows up during pregnancy. Which of course explains why regular people don’t have antibodies to that protein—they literally didn’t have the organ before becoming pregnant. And this something on the outside of placenta cells? That is a molecule called chondroitin sulfate (CS).
CS is one of these long molecules composed of repeating sugar units that I love to talk about. Unlike the sugars that we think of in terms of food and energy, sugar molecules like CS serve a lot of different functional roles on cell surfaces. CS is actually used in a lot of different normal human cell types for communication with other cells. But the CS on placental cells is special, called chondroitin sulfate A (CSA), because of a couple of modifications that scientists are still trying to figure out.
And this is when the story really gets interesting. Because the Salanti Lab at the University of Copenhagen in the Netherlands, whose researchers I heard speak at SDGS this past month, was trying to find a vaccine against this pregnancy-specific malaria by targeting CSA. And what they found was a new protein, called rVAR2, that attaches specifically to CSA. Being good scientists, they wanted to make sure that the protein would bind selectively to CSA. In other words, they wanted to make sure that their vaccine wouldn’t accidentally attack other healthy cells. They also had a suspicion that CSA might show up in other cell types. So they ran control experiments by trying to bind rVAR2 with a bunch of different lab grown cell types.
As they expected, the protein did not bind to any of the other healthy cells, proving again that CSA was only present on placenta in normal, healthy people. What they didn’t quite expect was that the protein bound very strongly to over 90% of the cancer cell lines they checked. This was astounding. So they double and triple checked their results, and they got a hold of as many cancerous cell lines as they could to validate their results. And the data held true. CSA which is normally found in placenta is also a highly selective marker for many different cancer types. The Salanti Lab is actually using these results to develop early screening techniques for some of the cancers that are currently hardest to diagnose. That paper is still in review, so I can’t talk about the specifics just yet.
What I can talk about is why on earth a cancer-selective marker would be found on placenta. Like cancer, the placenta is a quickly growing organ that has to essentially invade the organ that hosts it—namely the uterus. It is developed from temporary, foreign tissue associated with the fetus. So it kind of makes sense that both placenta and cancer would share a molecule that is known to help with cell to cell communication because both systems have to communicate with themselves and others about how to migrate and invade their host.
So in conclusion, pregnancy is a crazy, magical, bizarre system that we still have a lot to learn about. And maybe by learning more about the basics of human reproduction, we will even learn more about other aspects of human biology.
For the original paper on chondroitin sulfate in the placenta, click here.
For the original paper from the Salanti Lab, click here.